Scientists have found an essential component in the DNA repair process which could open the door to the development of new cancer drugs.
Researchers found hybrid structures composed of DNA and RNA play an important role in restoring the genetic information after the DNA is damaged. RNAs are short-lived copies of the genetic information stored in DNA.
The study also discovered that RNase H enzymes that target these hybrid structures are also essential for the efficient and precise repair of damaged DNA.
They showed that RNA-DNA hybrids form as part of the homologous-recombination (HR)-mediated DSB repair process and that RNase H enzymes are essential for their degradation and efficient completion of DNA repair.
Deleting RNase H stabilizes RNA-DNA hybrids around DSB sites and strongly impairs recruitment of the ssDNA-binding RPA complex. In contrast, overexpressing RNase H1 destabilizes these hybrids, leading to excessive strand resection and RPA recruitment and to severe loss of repeat regions around DSBs.
"This discovery opens the possibility for the development of new drugs that can target these enzymes, modulate their activity and block or enhance the efficiency of this important DNA repair pathway," senior author said.
Senior author said the accumulation of mutations in the human genome was the main driving force behind ageing-related diseases and cancer development.
"The better we understand these repair pathways, the more potential we have to modulate them and possibly develop some preventative methods to decrease the rate of the accumulation of various mutations," senior author said.
"RNase H enzymes have been studied and used in molecular biology for many years but their biological function was not entirely clear until now.
"Our study reveals that these enzymes are essential for DNA repair and this is probably one of their most important functions and the reason that they are present in every living cell."
Understanding DNA repair!
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